Respiratory Syncytial Virus (RSV) was discovered approximately 40 years ago, and was initially isolated from chimpanzees during an epizootic upper respiratory tract disease outbreak. RSV, which belongs to the family Paramyxoviridae, was subsequently found to be the most important cause of infectious pulmonary disease in human infants, and is a major causative agent of respiratory tract infections among children worldwide. Most children will be infected with RSV prior to their second birthday, leading to 75,000-125,000 hospitalizations and medical costs exceeding $650 million annually. Infants, immunocompromised children, or those with underlying respiratory disorders are at a particularly high risk of developing severe and lethal RSV respiratory tract infections that can be complicated by the resultant viral pneumonia and respiratory distress. Elderly and immune-compromised individuals are also susceptible to severe respiratory infections, thereby highlighting the importance of medical intervention in the form of early diagnosis and implementation of supportive or antiviral therapies.
There are only two FDA-approved drugs for use in patients having or at risk of RSV infection. Ribavirin is a nucleoside analog used for therapeutic intervention, which suffers from toxic liabilities that limit its use particularly in infants and children. SYNAGIS® (palivizumab) is a humanized monoclonal antibody to RSV. However it is expensive, used only for prophylaxis, and requires monthly injections. It is generally limited to use in high-risk pediatric patients. Due to the lack of a vaccine and the presence of toxicological limitations in existing therapies, there is substantial need for effective treatments with an improved profile.
While several small molecules have been developed for potential use in the treatment of RSV, all to date have failed to yield positive clinical results. Most of these small molecules appear to fall under the category of entry inhibitors which may result in the emergence of resistance. Therefore, the identification of a novel chemotype with an improved profile of efficacy and safety as compared to ribavirin may provide a stage for further development and better treatment options.